This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pharmaceutical research focusing on broad-spectrum antibiotics has declined significantly in recent years, despite the fact that drug resistance is increasing in many bacterial species. AstraZeneca is focusing its efforts in antibacterial research on novel targets with broad spectrum potential in efforts to create therapeutic agents with no cross-resistance to clinical strains of bacteria. In order to obtain these goals, protein crystallography is being utilized in most projects at all stages of the pipeline to guide inhibitor design, often with isozymes from multiple bacterial species. Protein crystallography is especially critical in the earliest stages of lead discovery, particularly with regard to fragment hits.Oncology targets at AstraZeneca R&D Boston include those accessible by structural efforts. Structure-based drug design is utilized in more than 50% of the oncology pipeline. Targets include, but are not limited to kinases, for which the wealth of available structural information from internal and external sources is critical in the design of potent and selective inhibitors.